Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update
- Study type
- Clinical guideline
- Study name
- ASCO 2026
- Design
- American Society of Clinical Oncology (ASCO) clinical practice guideline based on a systematic review; twelve new or updated randomised phase 3 trials were reviewed
- Source
- J Clin Oncol · 2026
In plain words
This guideline from the American Society of Clinical Oncology says that in advanced stomach and oesophageal cancer, tumour tests (PD-L1, HER2, MSI and claudin 18.2) should be done before treatment starts. If the tumour is PD-L1 positive, immunotherapy with chemotherapy is recommended; in HER2-positive tumours, trastuzumab is given with chemotherapy, and pembrolizumab is added if PD-L1 is also positive. If there is no marker that can be targeted, two-drug chemotherapy is the recommended treatment.
Key guideline recommendations
Results of testing for actionable biomarkers should be available as early as possible for treatment decision-making.
In pMMR patients with PD-L1 expression of 1 or higher, immunotherapy with doublet chemotherapy is recommended; patients with higher PD-L1 are more likely to benefit.
In gastroesophageal adenocarcinoma with PD-L1 below 1 and CLDN18.2 positivity, zolbetuximab is recommended; when both PD-L1 and CLDN18.2 are positive, shared decision-making is recommended.
In the absence of an actionable biomarker, or if the patient is not a candidate for targeted therapy or immunotherapy, doublet chemotherapy alone is recommended.
In HER2-positive, pMMR/MSS gastric or junctional adenocarcinoma, trastuzumab with doublet chemotherapy is recommended, with the addition of pembrolizumab if PD-L1 is 1 or higher.
In dMMR/MSI-H disease, immunotherapy alone or with doublet chemotherapy is recommended.
In the second line: ramucirumab with paclitaxel; trastuzumab deruxtecan in HER2-positive adenocarcinoma; and immunotherapy in oesophageal squamous cell carcinoma with PD-L1 of 1 or higher in patients who did not receive immunotherapy in the first line.
Study population
Patients with unresectable locally advanced, advanced or metastatic gastroesophageal cancer (adenocarcinoma of the stomach, gastroesophageal junction and oesophagus, and oesophageal squamous cell carcinoma).
Endpoints
This document is a guideline and has no trial endpoint; the recommendations were developed from a systematic review of phase 3 trials.
Safety and side effects
The abstract does not address treatment toxicity; details are in the full guideline.
Clinical significance and place in guidelines
This update makes a PD-L1 threshold of 1 or higher the basis for adding immunotherapy to first-line chemotherapy, assigns zolbetuximab to CLDN18.2-positive tumours with PD-L1 below 1, and proposes shared decision-making for tumours positive for both markers. ASCO maintains this guideline as a "living" guideline (version 2026.1.2 in August 2026).
Limitations
The abstract does not report the level of evidence or strength of the recommendations; these are given in the full guideline. The guideline covers only advanced disease and does not address perioperative treatment.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.